Advanced Neurology and Endocrinology. 1h 15m Robert Sapolsky video.
Genes code for proteins which in neurology critically means neurotransmitters and their receptors in the dendrites. So sociobiology, evolutionary theory, genetics, ethology (with its "innate releasing mechanisms"), all parts of the course so far, interrelate and feed into the brain's communication systems as neurology & endocrinology.
There are two major themes about neurology & endocrinology Sapolsky emphasizes 1) there are lots of different ways the nervous & endocrine systems can change their functions over time 2) there are lots of realms where individual differences can manifest (genetic & environmental). This lecture shows that the standard first-order understanding of neuroendocrinology hides much of the complexity, information tools used to organize our behavior, and signposts for individuality present in our exquisite biology.
This lecture is a bit involved, but it is still pretty high level with the goal of relaying just enough brain science to understand human behavior. My notes are extensive.
13. Advanced Neurology and Endocrinology
Neuroendocrinology: how hormones affect the neurons and neurons affect hormones
The limbic system: about emotion, affect & behavior (personality, temperment)
exocytosis: dumping neurotransmitters from their vesicles
Dale's law #2 (Henry Hallett Dale): each neuron has 1 characteristic type of neurotransmitter. In 1980's it was found that multiple neurotransmitters are released by some neurons (with a mixture of both/all types of neurotransmitters used by that neuron are stored in its vesicles). Some vesicles contain 3 types of neurotransmitters ("the world record"). This produces a potential for more information! The different neurotransmitters in a neuron's axon terminal tend to have different structures (one simple, one complex; one with a rapid short term effect, one with a slower long term effect which might mean changes to gene transcription). Interestingly it was found that we have receptors for the neurotransmitter on the axon terminal too: the transmitting neuron needs feedback on how much neurotransmitter is in the synapse.
ACTH: Adrenocorticotropic hormone also known as corticotropin
CRH: Corticotropin-releasing hormone also known as corticotropin-releasing factor (CRF)
Similar complexity is found in the endocrine system. In general neuro-endocrine axes work with the hypothalamus releasing a set of hormones to encode a pituitary response which then sends hormones into general circulation to signal receptors all over the body to respond appropriately. For the HPA axis (from the previous lecture: https://plus.google.com/104222466367230914966/posts/7RzgcWMoRBb), the hypothalamus releases NE (norepinephrine), E (epinephrine/adrenaline), OT (oxytocin), CRH, VP (vasopressin), and other hormones to the anterior pituitary (always depicted on the left) whose glands release ACTH to general circulation. The mixture of released hormones from the hypothalamus encode a stress signature enabling us to orchestrate and fine tune different responses to different types of stress. The shape of the secretory curve of ACTH differs with different signatures. In addition, the array of signature hormones can have other effects in the pituitary. Moreover, there is evidence for corticotropin inhibiting factors (best idea is peptide delta sleep-inducing factor (DSIP in Wikipedia): going to sleep may be a reasonable time to turn off the stress response?!
Dale's law #1: an action potential in a neuron will result in the release of neurotransmitter at every axon terminal. This principle is pretty well established. But Jerry Lettvin at MIT showed that you can have blockades that prevent the action potential from reaching some of the branches: neurons can regulate which of their branches get the message: more complexity = more information. There is an unexplored world of possible regulation mechanisms on the dendritic branches as well.
FSH=Follicle stimulating hormone
Specialized cells in the pituitary produce just one kind of hormone which are distributed throughout the gland. So there are local neighborhoods with distinct groupings of specialized cells. There is all sorts of communication between cells in the pituitary regulating output.
Negative feedback is needed to regulate all biological outputs including the release of hormones once the concentration / effects have reached some measured threshold (otherwise output would continue forever).
Autoreceptors for neurotransmitter occur on the axon terminal to provide measurments needed for negative feedback regulation. Sometimes one of the several neurotransmitters released by a neuron is there to do the bookkeeping by binding to autoreceptors. Similar behavior occurs in the neuroendocrine system to regulate hormones to reach set points (thresholds) with negative feedback to stop the release process by an inhibitory signal. Most endocrine negative feedback works by the brain measuring the amount of end product. Sometimes the brain measures not threshold amounts (which tends to be the focus later in the stress response process) but rates of change (particularly early in the stress response such as when the pituitary regulates ACTH: no one understands this mechanism which was predicted by Mary Dallman of UCSF in a theoretical study).
In biochemistry and pharmacology, a ligand is a substance that binds to a receptor which is a complex of proteins which in turn implies they are encoded by multiple genes implying that genetic variants are likely.
Autoregulation: adjusting receptors based on levels of ligands: so if the ligand signal is strong, we down regulate reception; if the ligand concentration is weak, we up regulate reception. There may even be autoregulatory effects in changing the autoreceptors.
SSRI: Selective serotonin reuptake inhibitor (such as Prozac)
Depression: may be caused by abnormalities in seratonin, dopamine, norepinephrine: SSRIs change blood concentrations, but only later does autoregulation change the number of receptors creating the delayed depression-improving effect.
Insulin resistance in adult onset diabetes: abnormality in insulin down regulation signaling to store away glucose leading to a cascade that eventually wears out the pancreas.
By choosing different protein mixes to build the receptor, changes in receptor regulation can be effected. Some receptor variation can be caused by a protein substitution that triggers high levels of excitation (epilepsy). Changes in the axon hillock's threshold can be caused by changes to the receptors in the dendrites. Similar issues affect hormone receptors.
As explained in the molecular genetics lecture (https://plus.google.com/104222466367230914966/posts/BK4xp8PFxav), steroid hormones have two parts: a hormone binding domain and a DNA binding domain (e.g., glucocorticoids, estrogen, progesterone, etc). Many steroid receptors have cofactors (another set of proteins that modify behavior in different cells). By changing the cofactors, a cell can induce different effects when their steroid ligands bind. Many receptors can bind more than one ligand. E.g., GABA, the main inhibitory neurotransmitter in mammals, has receptors consisting of a whole complex of proteins which include minor binding sites for 1) the major tranquilizers such as barbituates 2) the minor tranquilizers such as the benzodiazepines (such as Valium and Librium), and 3) derivatives of progesterone (seems to play a role in perimenstrual syndrome, PMS, which can effect mood alterations during the reproductive cycle of females). Binding these hormones potentiates GABA which increases its inhibitatory effects. GABA neurons form axoaxonic synapses which connect to the axon terminal of the neurons to which they project (instead of projecting to the dendrites as per standard neuroscience wiring schema). So instead of triggering a neural cascade the inhibitory neurons act to reduce the impact of the signaling of other neurons. So there must be GABA receptors on the axon (most neurotransmitter receptors live on the dendrites not on the axons). So GABA forms a neuromodulatory role by affecting upstream neurons not the neurons themselves.
Similarly some hormones can potentiate the effects of other hormones even though they may have no direct effects themselves.
Conclusion: the brain has lots of mechanisms for modulation of the "normal" first approximation to neural and endocrine signaling systems. These mechanisms give us lots of room for individual variability and lots of ways to respond to experience.